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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06384573




Registration number
NCT06384573
Ethics application status
Date submitted
22/04/2024
Date registered
25/04/2024
Date last updated
3/07/2024

Titles & IDs
Public title
DIAN-TU Amyloid Removal Trial (ART) in Dominantly Inherited Alzheimer's Disease
Scientific title
The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) Amyloid Removal Trial (ART): A Phase IIIb/IV Open-Label Study of Lecanemab to Evaluate Prevention and Progression of Dominantly Inherited Alzheimer's Disease
Secondary ID [1] 0 0
The Alzheimer's Association
Secondary ID [2] 0 0
DIAN-TU-003
Universal Trial Number (UTN)
Trial acronym
DIAN-TU
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Dementia 0 0
Alzheimer's Disease, Familial 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - lecanemab

Experimental: lecanemab - Starting at Week 0, participants will receive open-label lecanemab administered intravenously approximately every 2 weeks for a minimum of 5 years utilizing a common close design.


Treatment: Drugs: lecanemab
Administered intravenously
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The primary endpoint for the final analysis is the time to recurrent progression of Clinical Dementia Rating - Sum of Boxes (CDR-SB).
Timepoint [1] 0 0
Week 0, Week 52, Week 104, Week 156, Week 208, Week 260, Week 312, Week 364

Eligibility
Key inclusion criteria
Key

* Previously participated in the DIAN-TU-001 gantenerumab OLE period.
* Willing to participate in ongoing anti-amyloid therapy with informed consent by participant or legally authorized representative.
* People of childbearing potential (POCBP), if partner is not sterilized, must agree to use highly effective contraceptive measures (e.g., hormonal contraception, intra-uterine device, sexual abstinence, vasectomized partner) from Consent (V1) until five (5) halflives after last dose of any study drug. Refer to the study procedures manual for acceptable methods of contraception.
* Co-enrollment in the DIAN Observational Study (DIAN Obs, NCT00869817) and is willing to complete DIAN Obs procedures and assessments.
* Able to undergo safety MRI scans as required.
* Vascular access adequate for study drug administration and safety monitoring.

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has any significantly increased risks associated with amyloid-related imaging abnormalities characterized by edema/effusion (ARIA-E), ARIA characterized by microhemorrhage (ARIA-H MCH) or superficial siderosis (ARIA-H SS) and vascular factors reviewed by the medical monitoring team. Risks to be reviewed include:

1. History of recurrent ARIA-E (2 or more episodes regardless of location).
2. More than 20 ARIA-H MCH.
3. More than one area of ARIA-H SS.
4. More than 2 lacunar infarcts or stroke involving a major vascular territory.
* Requiring full anticoagulation or on high dose or dual antiplatelet therapy (daily aspirin 325 mg or less allowed).
* History of macrohemorrhages >1 cm.
* Intolerance for lecanemab.
* Pregnancy.
* Breastfeeding.
* Uncontrolled medical condition that is life threatening or precludes interpretation of AD.
* Uncontrolled blood pressure including mean arterial pressure exceeding 97 mm Hg.
* Uncontrolled seizure disorder.
* Ongoing auto-immune condition, bleeding diathesis, or neutropenia (platelets lower than 50,000) major depression or psychiatric condition.
* Exposure to other AD investigational agents within the past six months, or five half-lives from Visit 2 (Entry Visit) whichever is longer.
* Active cancer/malignancy that could interfere with study evaluations.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/06/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2029
Actual
Sample size
Target
65
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Neuroscience Research Australia - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
Washington
Country [5] 0 0
United Kingdom
State/province [5] 0 0
Greater London

Funding & Sponsors
Primary sponsor type
Other
Name
Washington University School of Medicine
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Alzheimer's Association
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
Eisai Inc.
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is an open label study to treat dominantly inherited Alzheimer's disease (DIAD) mutation carrier participants from the DIAN-TU-001 gantenerumab Open Label Extension (OLE) period with lecanemab to determine the effects of amyloid removal on age of onset and clinical progression compared to external controls, if amyloid plaque as measured by amyloid PET can be fully removed in DIAD, and the effects of amyloid removal on biomarkers of disease progression.
Trial website
https://clinicaltrials.gov/study/NCT06384573
Trial related presentations / publications
Salloway S, Farlow M, McDade E, Clifford DB, Wang G, Llibre-Guerra JJ, Hitchcock JM, Mills SL, Santacruz AM, Aschenbrenner AJ, Hassenstab J, Benzinger TLS, Gordon BA, Fagan AM, Coalier KA, Cruchaga C, Goate AA, Perrin RJ, Xiong C, Li Y, Morris JC, Snider BJ, Mummery C, Surti GM, Hannequin D, Wallon D, Berman SB, Lah JJ, Jimenez-Velazquez IZ, Roberson ED, van Dyck CH, Honig LS, Sanchez-Valle R, Brooks WS, Gauthier S, Galasko DR, Masters CL, Brosch JR, Hsiung GR, Jayadev S, Formaglio M, Masellis M, Clarnette R, Pariente J, Dubois B, Pasquier F, Jack CR Jr, Koeppe R, Snyder PJ, Aisen PS, Thomas RG, Berry SM, Wendelberger BA, Andersen SW, Holdridge KC, Mintun MA, Yaari R, Sims JR, Baudler M, Delmar P, Doody RS, Fontoura P, Giacobino C, Kerchner GA, Bateman RJ; Dominantly Inherited Alzheimer Network-Trials Unit. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease. Nat Med. 2021 Jul;27(7):1187-1196. doi: 10.1038/s41591-021-01369-8. Epub 2021 Jun 21.
Bateman RJ, Aisen PS, De Strooper B, Fox NC, Lemere CA, Ringman JM, Salloway S, Sperling RA, Windisch M, Xiong C. Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease. Alzheimers Res Ther. 2011 Jan 6;3(1):1. doi: 10.1186/alzrt59.
Morris JC, Aisen PS, Bateman RJ, Benzinger TL, Cairns NJ, Fagan AM, Ghetti B, Goate AM, Holtzman DM, Klunk WE, McDade E, Marcus DS, Martins RN, Masters CL, Mayeux R, Oliver A, Quaid K, Ringman JM, Rossor MN, Salloway S, Schofield PR, Selsor NJ, Sperling RA, Weiner MW, Xiong C, Moulder KL, Buckles VD. Developing an international network for Alzheimer research: The Dominantly Inherited Alzheimer Network. Clin Investig (Lond). 2012 Oct 1;2(10):975-984. doi: 10.4155/cli.12.93.
Moulder KL, Snider BJ, Mills SL, Buckles VD, Santacruz AM, Bateman RJ, Morris JC. Dominantly Inherited Alzheimer Network: facilitating research and clinical trials. Alzheimers Res Ther. 2013 Oct 17;5(5):48. doi: 10.1186/alzrt213. eCollection 2013.
Mills SM, Mallmann J, Santacruz AM, Fuqua A, Carril M, Aisen PS, Althage MC, Belyew S, Benzinger TL, Brooks WS, Buckles VD, Cairns NJ, Clifford D, Danek A, Fagan AM, Farlow M, Fox N, Ghetti B, Goate AM, Heinrichs D, Hornbeck R, Jack C, Jucker M, Klunk WE, Marcus DS, Martins RN, Masters CM, Mayeux R, McDade E, Morris JC, Oliver A, Ringman JM, Rossor MN, Salloway S, Schofield PR, Snider J, Snyder P, Sperling RA, Stewart C, Thomas RG, Xiong C, Bateman RJ. Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial. Rev Neurol (Paris). 2013 Oct;169(10):737-43. doi: 10.1016/j.neurol.2013.07.017. Epub 2013 Sep 6.
McDade E, Cummings JL, Dhadda S, Swanson CJ, Reyderman L, Kanekiyo M, Koyama A, Irizarry M, Kramer LD, Bateman RJ. Lecanemab in patients with early Alzheimer's disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study. Alzheimers Res Ther. 2022 Dec 21;14(1):191. doi: 10.1186/s13195-022-01124-2.
van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer LD, Iwatsubo T. Lecanemab in Early Alzheimer's Disease. N Engl J Med. 2023 Jan 5;388(1):9-21. doi: 10.1056/NEJMoa2212948. Epub 2022 Nov 29.
Ryman DC, Acosta-Baena N, Aisen PS, Bird T, Danek A, Fox NC, Goate A, Frommelt P, Ghetti B, Langbaum JB, Lopera F, Martins R, Masters CL, Mayeux RP, McDade E, Moreno S, Reiman EM, Ringman JM, Salloway S, Schofield PR, Sperling R, Tariot PN, Xiong C, Morris JC, Bateman RJ; Dominantly Inherited Alzheimer Network. Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology. 2014 Jul 15;83(3):253-60. doi: 10.1212/WNL.0000000000000596. Epub 2014 Jun 13.
Public notes

Contacts
Principal investigator
Name 0 0
Randall J Bateman, MD
Address 0 0
Washington University School of Medicine
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jamie Bartzel, MA
Address 0 0
Country 0 0
Phone 0 0
844-DIANEXR (342-6397)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06384573